Sarcopenia Is a Cause and Consequence of Metabolic Dysregulation in Aging Humans: Effects of Gut Dysbiosis, Glucose Dysregulation, Diet and Lifestyle

Abstract

Skeletal muscle mass plays a critical role in a healthy lifespan by helping to regulate glucose homeostasis. As seen in sarcopenia, decreased skeletal muscle mass impairs glucose homeostasis, but it may also be caused by glucose dysregulation. Gut microbiota modulates lipopolysaccharide (LPS) production, short-chain fatty acids (SCFA), and various metabolites that affect the host metabolism, including skeletal muscle tissues, and may have a role in the sarcopenia etiology. Here, we aimed to review the relationship between skeletal muscle mass, glucose homeostasis, and gut microbiota, and the effect of consuming probiotics and prebiotics on the development and pathological consequences of sarcopenia in the aging human population. This review includes discussions about the effects of glucose metabolism and gut microbiota on skeletal muscle mass and sarcopenia and the interaction of dietary intake, physical activity, and gut microbiome to influence sarcopenia through modulating the gut-muscle axis. Emerging evidence suggests that the microbiome can regulate both skeletal muscle mass and function, in part through modulating the metabolisms of short-chain fatty acids and branch-chain amino acids that might act directly on muscle in humans or indirectly through the brain and liver. Dietary factors such as fats, proteins, and indigestible carbohydrates and lifestyle interventions such as exercise, smoking, and alcohol intake can both help and hinder the putative gut-muscle axis. The evidence presented in this review suggests that loss of muscle mass and function are not an inevitable consequence of the aging process, and that dietary and lifestyle interventions may prevent or delay sarcopenia.

Keywords: glucose metabolism; gut microbiome; gut microbiota-muscle axis; inflammation; short-chain fatty acids; skeletal muscle mass.

Figure 1

Proposed interactions of diet and lifestyle with skeletal muscle and glucose metabolism. Effects of diet and lifestyle on skeletal muscle mass and function and the impact on blood glucose regulation are explained; diet and lifestyle are shown to exert effects on muscle mass and function, which have interactive effects on glucose metabolism. Sirt 1, NAD-dependent deacetylase sirtuin-1; PGC-1α, peroxisome proliferator-activated receptor-gamma coactivator 1α; mTORC1, mechanistic target of rapamycin C1; S6K1, ribosomal protein S6 kinase beta-1; MAPK, mitogen-activated protein kinase; ERK1/2, extracellular signal-regulated kinases; AMPK, AMP-activated protein kinase; PI3K, phosphoinositide 3-kinase; AKT; NAD⁺, nicotinamide adenine dinucleotide.

Figure 2

Proposed interaction of gut bacteria with glucose metabolism. Effects of gut microbiota and their products on the liver, gut cell wall, adipocytes, and inflammation as regulators of glucose metabolism are explained; gut bacteria can increase and decrease inflammation, either improving or exacerbating insulin resistance and muscle loss. LPS, lipopolysaccharide; TNF-α, tumor necrosis factor-α; IL-6, interleukin-6.